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Immature poxviruses are characterized by nonicosahedral semiordered protein scaffolds critical for morphogenesis. Here, the authors use cryo-EM structures of Vaccinia virus D13 scaffold intermediates to explain their assembly mechanism.

Local activity of the DNA methylation machinery remains poorly understood. Here, the authors present a theoretical and experimental framework to infer methylation and demethylation rates at genome scale in mouse embryonic stem cells, finding that maintenance methylation activity is reduced at transcription factor binding sites, while methylation turnover is elevated in transcribed gene bodies.

Hydrogels incorporating human stromal cells and that after implantation in mice recruit cells from an orthotopic human tumour xenograft enable, after the injection of human immune cells, the study of the evolution of pre-metastatic niches.

In the absence of progranulin, microglia enter a disease-specific state that causes endolysosomal dysfunction and neurodegeneration, and these microglia promote TDP-43 granule formation, nuclear pore defects and cell death specifically in excitatory neurons via the complement activation pathway.

Despite major drug discovery efforts, the therapeutic options for glioblastoma (GBM) remain inadequate. Here they analyze patient-derived xenograft model of GBM to quantitatively map distribution and cellular response to the EGFR inhibitor erlotinib, and report heterogeneous erlotinib delivery to intracranial tumors to be inadequate to inhibit EGFR signaling.

Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

In chronic lymphocytic leukemia (CLL), evolution is driven by transcriptional and epigenetic heterogeneity. Here, the authors integrate epigenomic analyses to show how intra-tumoral epigenetic diversity results in divergent chromatin states in CLL cells, increasing cell-to-cell transcriptional heterogeneity.

The genome of Ectocarpus siliculosis, a model for the study of brown algae, has been sequenced. These seaweeds are complex photosynthetic organisms that have adapted to rocky coastal environments. Genome analysis sheds light on this adaptation, revealing an extended set of light-harvesting and pigment biosynthesis genes, and new metabolic processes such as halide metabolism. Comparative analyses are also significant with respect to the evolution of multicellularity in plants, animals and brown algae.

Fe₃Sn₂ hosts massive Dirac fermions, owing to the underlying symmetry properties of the bilayer kagome lattice in the ferromagnetic state and the atomic spin–orbit coupling.

Solutions of computations can be encoded in the ground state of many-body spin models. Here the authors show that solutions to generic reversible classical computations can be encoded in the ground state of a vertex model, which can be reached without finite temperature phase transitions.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Systems level analysis finds two transcription factors, Rv0324 and Rv0880, are required for Mycobacterium tuberculosis tolerance to bedaquiline.

Copy number variants (CNVs) account for a major proportion of human genetic diversity and may contribute to genetic susceptibility to disease. Here, a large, genome-wide study of association between common CNVs and eight common human diseases is presented. The study provides a wealth of technical insights that will inform future study design and analysis. The results also indicate that common CNVs that can be 'typed' on existing platforms are unlikely to contribute much to the genetic basis of common diseases.

Application of next-generation sequencing using the ABI SOLiD technology to mammalian transcriptome analysis enabled a survey of the content, the complexity and the developmental dynamics of the embryonic stem cell transcriptome in the mouse. Also in this issue, Mortazavi et al. report Illumina technology–based RNA-Seq analysis of the mouse transcriptome in three different tissues.

A combination of genetic tricks and fancy fluorescent proteins is used to develop the Technicolor version of Golgi staining, 'Brainbow', in which hundreds of individual neurons are painted, each with a distinctive hue. This technology should not only boost mapping efforts in normal or diseased brains, but could also be applied to other complex cell populations, such as the immune system.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

The most abundant RNA modification in humans, m⁶A, can be installed at specified RNA sequences in cells, enabling functional studies.

Studies of the functional organization of the prefrontal cortex have produced contradicting results depending on the task used. Here, Riley and colleagues demonstrate that prefrontal areas are specialized across the anterior posterior axis and that the effects of the task themselves impact more the anterior areas.

Rearrangements of the Ig loci are essential for generating antibody diversity but abnormal translocations can be a driving event for myeloma. Here Walker et al. perform whole exome sequencing on myeloma patients to capture the diversity of mutational changes.

Artificially engineered tissues may be useful for regenerative therapies but their fabrication tends to be complicated. Stevens et al. present a technique for the precise organization of microstructurally complex tissues that works with a variety of cell types and does not require sophisticated equipment.

In this study, the authors show that the spatial responses of populations of grid cells are constrained to a two-dimensional activity manifold, and the relationships between pairs of grid cells are resistant to perturbation. These findings provide evidence of low-dimensional continuous attractor dynamics in the network.

Griffin et al. present a versatile method for scalable and low-cost sequencing for the construction of epigenetic clocks. They assay 2,892 human or mouse samples, benchmark their method and assess diverse interventions.

Using primer-exchange reactions, SABER extends FISH probes with repetitive sequences that can accommodate multiple fluorescent imager strands, resulting in up to 450-fold signal amplification. SABER is showcased in DNA and RNA FISH experiments across a range of complex biological samples.

An anion and metal ion template is used to form woven polymer patches that are joined together by polymerization into a fully woven, two-dimensional, molecular patchwork.

The ejection sites of the martian meteorites are still unknown. Here, the authors build a database of 90 million craters and show that Tharsis region is the most likely source of depleted shergottites ejected 1.1 Ma ago, thus confirming that some portions of the mantle were recently anomalously hot.

Wolf Reik and Ian Dunham and colleagues cloned and sequenced the complete IGF2-H19 locus in tammar wallaby, a marsupial. Functional analyses revealed conservation of imprinting mechanisms, including germline DNA methylation, between marsupials and eutherians.

Temporal regulation of embryonic neurogenesis is controlled by hypostable transcription factors. Here the authors show that the RNase III Drosha and DGCR8/Pasha, key components of the microRNA (miRNA) microprocessor, have important functions in mouse neurogenesis. Their results suggest direct and miRNA-independent destabilization of proneural mRNAs by the microprocessor.

H2AX phosphorylation is an early response to DNA damage and is mediated by the ATM/ATR kinases. By examining the genome-wide location of γ-H2A in wild type and mutant S. cerevisiae strains, loci that tend to engage ATR (Mec1) and ATM (Tel1) are identified as a route to mapping fragile sites in this genome.

Castration-resistant prostate cancer frequently presents with persistent androgen receptor signalling. Here, the authors find that the androgen receptor is subject to genetic rearrangements, resulting in variants with ligand-independent activity.

Preeclampsia, a hypertension condition with no approved therapies, is treated in monkeys by gene silencing in the placenta.

Leprosy is caused by the yet-uncultured pathogen Mycobacterium leprae. Here, Benjak et al. obtain M. leprae genome sequences from DNA extracted from patients' skin biopsies and, by analysing 154 genomes from 25 countries, provide insight into the pathogen’s evolution and antimicrobial resistance.

Combining CRISPRi-FlowFISH to perturb enhancers with an activity-by-contact model to predict complex connections allows systematic mapping of enhancer–gene connections in a given cell type, on the basis of chromatin-state measurements.

Electrons are confined to an artificial Sierpiński triangle. Microscopy measurements show that their wavefunctions become self-similar and their quantum properties inherit a non-integer dimension between 1 and 2.

Cell competition is a quality control mechanism to eliminate unfit cells. Here the authors show that physical compaction of less fit cells surrounded by healthy neighbours leads to increased expression of tumour suppressor p53 in the compacted cells, causing cell death.

Osteogenesis imperfecta (OI) is genetically linked to autosomal dominant or autosomal recessive mutations. Here, Marini et al. describe two families with X-chromosome-linked OI with mutations in MBTPS2 that alter regulated intramembrane proteolysis and subsequent defects in collagen crosslinking and osteoblast function.

Ferroelectric switching is studied in PbZr_0.2Ti_0.8O₃ thin films. Nanotwinned ferroelectric domains with broadened switching characteristics are observed and control over ferroelectric switching is demonstrated.

Topoisomerase 1 (Top1) inhibition is believed to mediate cellular toxicity by trapping Top1 on nicked DNA, leading to double-strand break formation during replication. New studies show that clinically relevant doses of Top1 poisons lead instead to extensive replication-fork reversal that is mediated by Poly(ADP-ribose) polymerases, limiting double-strand break formation.

Evan Eichler and colleagues identify a recurrent microdeletion on 16p12.1 associated with developmental, cognitive and neuropsychiatric phenotypes. They also show that more severe phenotypes are frequently correlated with the presence of a second large genomic rearrangement, supporting a complex model of pathogenesis that may underlie the variable expressivity typical of many microdeletion syndromes.

In mouse, an axonal connectivity map showing the wiring patterns across the entire brain has been created using an EGFP-expressing adeno-associated virus tracing technique, providing the first such whole-brain map for a vertebrate species.

Most mammalian promoters are inherently bidirectional, but transcription only elongates productively in one direction. Data presented in this paper demonstrate that at least part of the answer lies in the asymmetric distribution of polyadenylation-site sequences around human gene promoters causing termination of upstream antisense transcription.

It is thought that Atlantic style passive margins have experienced episodes of uplift and volcanism in response to changes in mantle circulation. The authors here employ U-Pb dating of calcite in faults and fractures along the eastern North American margin and find a 40 Myr long period of fracturing and faulting from 115 to 75 Ma.

Acquired resistance is a major problem in cancer immunotherapy. Here the authors report a study of two patients with Merkel cell carcinoma under immunotherapy treatment who develop resistance after deep responses for >1 year and identified a novel mechanism of acquired, gene-specific transcriptional suppression of HLAs.